The field of tissue engineering has tantalizingly offered the possibility of regenerating new tissue in order to treat a multitude of diseases and conditions within the human body. Nevertheless, in spite of significant progress with
in vitro
and small animal studies, progress toward realizing the clinical and commercial endpoints has been slow and many would argue that ultimate goals, especially in treating those conditions which, as yet, do not have acceptable conventional therapies, may never be reached because of flawed scientific rationale. In other words, sustainable tissue engineering may not be achievable with current approaches. One of the major factors here is the choice of biomaterial that is intended, through its use as a “scaffold,” to guide the regeneration process. For many years, effective specifications for these biomaterials have not been well-articulated, and the requirements for biodegradability and prior FDA approval for use in medical devices, have dominated material selection processes. This essay argues that these considerations are not only wrong in principle but counter-productive in practice. Materials, such as many synthetic bioabsorbable polymers, which are designed to have no biological activity that could stimulate target cells to express new and appropriate tissue, will not be effective. It is argued here that a traditional ‘scaffold’ represents the wrong approach, and that tissue-engineering templates that are designed to replicate the niche, or microenvironment, of these target cells are much more likely to succeed.